Authors: Isaac J. Perron, Allan I. Pack, Sigrid Veasey

Brief in Brief (TL;DR)

What do we know:
Obese people are more likely to be excessively tired during the day compared to their lean counterparts, but it is not clear why. This problem has been studied in mice, which are made obese by feeding them a high-fat diet, or HFD for short. Multiple reports have found HFD-fed obese mice have trouble staying awake and sleep much more than mice fed a low-calorie, regular diet (RD).

What don’t we know:
Are obese mice sleepy because they are eating the HFD or because they are obese? And how can you separate these effects anyway?

What this study shows:
The researchers made up a 'diet switch' food program, switching obese mice to a RD and skinny mice to a HFD, and studied the sleep patterns of the two mouse groups when they were of equal weights. The formerly-skinny mice switched to the HFD had the classic sleep problems observed in obese mice, while the formerly-obese mice switched to RD slept normally. Thus, when it comes to sleep and wakefulness, your diet is a more important factor than what your weight on the scale reads.

What we can do in the future because of this study:
Future work can investigate which types of food (e.g., fat vs carbohydrates vs protein) cause sleep problems, and whether other methods of weight loss (such as exercise) can also fix sleep issues. Also, researchers can use the 'diet switch' food program to figure out what else is affected by diet separate from body weight.

Why you should care:
Morbid obesity means that weight gain has become so severe that it is now considered a disease. One issue obese people face is excessive sleepiness. This research shows that beginning to lose weight by healthy eating can reverse this tiredness, even before all the weight is lost.

Brief for Non-Neuroscientists

Despite the high prevalence of obesity in the United States, many people are unaware of the strong association between obesity and excessive daytime sleepiness (EDS). Remarkably, obese patients who undergo bariatric surgery for weight loss report dramatic improvements in EDS before significant weight loss occurs, suggesting that other factors besides excess weight may contribute to daytime wake impairments. We hypothesize that the initiation of weight gain/loss due to changes in energy balance (calories ingested versus calories burned) can profoundly affect sleep and wakefulness, which may contribute to EDS in obese people.

Our lab models human obesity by feeding normal mice a diet enriched with fat (a.k.a. 'high fat diet', or HFD). Similar to humans, obese mice are unable to stay awake for long periods of time and spend more time asleep when their non-obese counterparts are most active. However, no study to date has been able to separate the effects of energy balance (i.e., weight gain/loss) from body weight on sleep/wake impairments.

To accomplish this, we designed an experiment that caused lean mice to gain weight and obese mice to lose weight; when body weight was similar between the two groups, we measured their sleep/wake behavior. We found that obese mice that had been switched to a normal diet lost weight and exhibited increased wake time and improved sleep/wake quality compared to lean mice gaining weight from HFD consumption, even though these two groups of mice had no differences in their body weight. Therefore, this study supports the hypothesis that modifying energy balance via dietary changes is sufficient to induce or reverse EDS in mice, independent of their body weight. These results are especially relevant to people, both obese and non-obese, who need to be alert, awake, and focused during the day (e.g., truck drivers, medical doctors, and airplane pilots).

Brief for Neuroscientists

Excessive daytime sleepiness commonly affects obese people, even in those without sleep apnea or other sleep disorders, yet its underlying mechanisms remain uncertain. Follow-up studies with obese patients who have undergone bariatric surgery for weight loss report significant improvements in daytime wakefulness, even though these patients are still obese. This suggests that obesity per se may not be the primary determinant in regulation of sleep and wakefulness. We implemented a novel feeding paradigm in mice that generates two groups with equal body weight but opposing energetic balance to test the relative importance of diet versus body weight. Two subsets of mice consuming either a normocaloric regular diet (RD) or hypercaloric high-fat diet (HFD) for 8 weeks were switched to the opposite diet for 1 week. One week later, these two groups of mice were of similar weight, although they were in diametrically opposed energetic statuses due to their respective diets. We found that animals switched to HFD (and thus gaining weight) had decreased wake time, increased NREM sleep time, and worsened sleep/wake fragmentation compared to mice switched to RC (which were in weight loss). These effects were driven by significant sleep/wake changes induced by acute dietary manipulations (during the week after the diet change). Sleep homeostasis, as measured by delta power increase following sleep deprivation, was unaffected by our feeding paradigm. Thus, acute dietary manipulations are sufficient to alter sleep and wakefulness independent of body weight and without effects on sleep homeostasis.